莫努匹韦对 COVID-19 生物标志物、呼吸干预和医疗服务的影响：一项随机、安慰剂对照试验。
Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial.
机构信息
Merck & Co., Inc., Rahway, New Jersey (M.G.J., A.P., Y.Z., H.W., A.W., M.L.B., A.P., C.D.).
Fundacion Valle del Lili, Cali, Colombia (P.A.M.).
出版信息
Ann Intern Med. 2022 Aug;175(8):1126-1134. doi: 10.7326/M22-0729. Epub 2022 Jun 7.
BACKGROUND
In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease.
OBJECTIVE
To identify other potential clinical benefits of molnupiravir versus placebo.
DESIGN
Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597).
SETTING
107 sites globally.
PARTICIPANTS
1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19.
INTERVENTION
Molnupiravir, 800 mg, or placebo every 12 hours for 5 days.
MEASUREMENTS
Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo ), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization.
RESULTS
Participants receiving molnupiravir showed faster normalization of CRP and Spo , with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19-related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants.
LIMITATIONS
Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2.
CONCLUSION
The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death.
PRIMARY FUNDING SOURCE
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
背景
在 MOVe-OUT 试验中，莫努匹韦显示出对患有轻度至中度 COVID-19 和有进展为重症疾病风险因素的成年人住院或死亡风险的具有临床意义的降低。
目的
确定莫努匹韦相对于安慰剂的其他潜在临床获益。
设计
MOVe-OUT 随机、双盲、安慰剂对照 3 期部分的二次分析。（ClinicalTrials.gov：NCT04575597）。
设置
全球 107 个地点。
参与者
1433 名年龄在 18 岁或以上的非住院成年人，患有轻度至中度 COVID-19。
干预措施
莫努匹韦，800 mg，或安慰剂，每 12 小时服用一次，持续 5 天。
测量
从基线到第 29 天的所有随机分配参与者的 C-反应蛋白（CRP）浓度和氧饱和度（Spo ）变化、呼吸干预（包括有创机械通气）的需要以及所有接受治疗的参与者的医疗服务需求，以及在随机分组后住院的参与者亚组中呼吸干预和出院时间的需要。
结果
与安慰剂相比，接受莫努匹韦治疗的参与者更快地使 CRP 和 Spo 恢复正常，在治疗第 3 天就观察到改善。与安慰剂相比，接受莫努匹韦治疗的参与者需要呼吸干预的需求减少（相对风险降低[RRR]，34.3%[95%CI，4.3%至 54.9%]），在随机分组后住院的参与者中也有类似的发现（RRR，21.3%[CI，0.2%至 38.0%]）。接受莫努匹韦治疗的住院参与者比接受安慰剂治疗的参与者中位数提前 3 天出院。急性护理就诊（7.2%比 10.6%；RRR，32.1%[CI，4.4%至 51.7%]）和 COVID-19 相关的急性护理就诊（6.6%比 10.0%；RRR，33.8%[CI，5.6%至 53.6%]）在接受莫努匹韦治疗的参与者中较少发生。
局限性
一些分析是事后进行的。莫努匹韦治疗的长期获益未得到评估。参与者未接种 SARS-CoV-2 疫苗。
结论
研究结果表明，莫努匹韦除了降低住院或死亡风险外，还有其他重要的临床获益。
主要资金来源
默克 Sharp & Dohme LLC，默克公司的子公司。
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